Diffusion MRI with Rotation-Invariant Spherical Harmonic Decomposition for Characterizing Complex Fiber Structures in the Brain We proposed a new rotation-invariant spherical harmonic decomposition (SHD) method for analyzing high angular resolution diffusion (HARD) imaging. Regular SHD methods have been used to characterize the features of the apparent diffusion coefficient (ADC) profile measured by the HARD technique. However, these regular SHD methods are rotation-variant, i.e. the magnitude and/or the phase of the harmonic components changes with the rotation of the ADC profile. We propose a new rotation-invariant SHD (RI-SHD) method based on the rotation-invariant property of a diffusion tensor model. The basic idea of the proposed method is to reorient the measured ADC profile into a local coordinate system determined by the three eigenvectors of the diffusion tensor in each imaging voxel, and then apply a SHD to the ADC profile. Both simulations and in vivo experiments were carried out to validate the method. The proposed RI-SHD method is superior in characterizing the diffusion patterns of multiple fiber structures between different brain regions or across subjects. Simultaneous Measurements of Functional MRI signals Based on Blood Volume, Blood Flow, and Blood Oxygenation Changes during Brain Activation We proposed a novel imaging technique for measuring VASO, ASL perfusion and BOLD signals in a single scan. Functional imaging experiments with visual stimulation paradigms demonstrated the feasibility of this technique, and showed its significant improvement in CNR per unit time compared to those acquired individually with conventional techniques. Furthermore, the new technique was able to obtain transient information of activation-induced functional signals in event-related functional experiments. With efficient measurement of three complementary functional signals associated with brain activation, this technique will provide a valuable tool to assist with data interpretation and functional transduction mechanisms. Nonlinearity of Blood Volume, Blood Flow, and Blood Oxygenation signals during Increased Brain Activity We further assessed the linearity of VASO, ASL and BOLD signals using the abovementioned imaging technique that acquires these functional signals in a single scan. Analysis of the blood volume, blood flow, and blood oxygenation based responses to various stimulus durations showed that nonlinearity is present in these three signals to brief stimuli (< 4 s), and the degree of nonlinearity increases with decreased stimulus duration. VASO and ASL perfusion signals exhibit very similar nonlinear properties, while BOLD demonstrated a stronger degree of nonlinearity than VASO and ASL. Information on the linearity of the hemodynamic signals will be useful for better design of stimulation paradigms and for more accurate interpretation of fMRI data. Head-Motion Suppression Using Real-Time Feedback of Motion Information and its Effects on Task Performance in fMRI We developed a voluntary head-motion suppression method using feedback to subjects of their own head motion information. A real-time fMRI system was developed on standard MR imaging hardware for this purpose. The head-motion information was simplified as a four-way arrow display that changed color from green to red when a composite head motion index went beyond a specified threshold. The arrow indicators were integrated into a version of the commonly used visual N-BACK task. Results suggest a significant suppression of head motion consistently in all subjects while the influence on task performance and brain activation was minimal. It is proposed that under certain experimental conditions, voluntary head motion suppression may feasibly be employed without significant compromise of fMRI data. Mapping Rat Brain Activity Induced by Acute Cocaine Administration Using Dynamic Manganese-Enhanced MRI. The goal of functional neuroimaging is to observe neuronal activity. However, most current fMRI BOLD techniques indirectly measure neuronal activity through hemodynamic responses coupled to neuronal and metabolic changes. Action potential is a characteristic of neuronal activity, during which changes in resting membrane potential lead to an increase of conductance in voltage gated Ca2+ channels and influx of Ca2+ ions. Previous study demonstrated that Mn2+ can substitute for Ca2+ and enters neurons via the same voltage gated Ca2+ channels. Mn2+ is paramagnetic, and is MRI sensitive. We have applied manganese-enhanced MRI to map neuronal activity under acute cocaine challenges. Experiments were conducted at a Bruker 9.4T animal MR scanner. Results show that this is a very promising tool for mapping drug-induced neuronal activity.